This proposal seeks funds to purchase an Olympus FV1000MPE multiphoton microscope to be used as the main instrument in a core facility at the Weill Cornell Medical College. The core facility serves translational and basic medical science investigators. In addition to investigators at Weill Cornell, researchers from the Hospital for Special Surgery will be users of the facility. Additionally, this instrument will serve as the major instrument for a large collaborative project with scientists at Cornell University in Ithaca who are developing novel methods, including multiphoton endoscopy, for use in human patient care. This collaborative project is also a component of the Clinical and Translational Science Center Project based at Weill Cornell. The largest user of the facility will be a collaborative group of surgeons, pathologists, microscopists, engineers, and physicists who are examining unstained fresh human biopsy samples to create an atlas of normal and diseased human tissue as seen by autofluorescence and second harmonic generation. Preliminary data suggest that such images can provide diagnostic information comparable to conventional histopathology for certain types of cancers. SHG from collagen will also be used for examining human bone biopsy specimens for studies of osteoporosis. Several studies will carry out imaging in living animals, and several of these projects will benefit from synergistic interactions based on the use of the FV1000MPE. For example, three investigators will examine events in the brain, and two of these collaborate on studies of the formation and degradation of Alzheimer's disease amyloid plaques. Two projects will examine macrophages and dendritic cells in mice and will investigate properties such as cell migration. The FV1000MPE is very well suited to serve the needs of this group of investigators. It has superb optics that are optimized for multiphoton microscopy and for relatively effective imaging deep into tissue. It is easy to use, which will allow rapid training of investigators with diverse backgrounds. The microprobe objectives are very advantageous for imaging in animals because of their small diameter, and these will also be very useful for examination of irregularly shaped surgical specimens, which cannot be cut or altered before being sent for pathology processing.